Mapping Subcortical Motor Pathways in Humans with Startle-conditioned TMS

Subcortical motor pathways, such as the reticulospinal tract, are critical for producing and modulating voluntary movements and have been implicated in neurological conditions. Previous research has described the presence of ipsilateral motor evoked potentials (iMEPs) in the arm to transcranial magentic stimulation (TMS), and suggested they could be mediated by the uncrossed corticospinal tract or by ipsilateral cortico-reticulospinal connections. Here, we sought to elucidate the role of the reticulospinal tract in mediating iMEPs by assessing their modulation by a startling acoustic stimulus and mapping these responses across multiple upper limb effectors. In a first experiment, we delivered TMS at various intervals (1, 5, 10 and 15 ms) after a startling acoustic stimulus, known to excite the reticular formation, to elicit iMEPs in the arm. We observed robust facilitation of iMEP area when startle conditioning preceded TMS at the 10 ms interval. In a second experiment, we replicated our findings showing that both the area and number of iMEPs in the arm increases with startle conditioning. Using this technique, we observed that iMEPs are more prominent in the arm compared with the hand. In a third experiment, we also observed greater presence of iMEPs in flexor compared with extensor muscles. Together, these findings are consistent with properties of the reticulospinal tract observed in animals, suggesting that iMEPs primarily reflect reticulospinal activity. Our findings imply that we can use this approach to track modulation of cortico-reticulospinal excitability following interventions or neurological conditions where the reticulospinal tract may be involved in motor recovery.